HCV core protein and virus assembly: what we know without structures.

HCV core protein and virus assembly: what we know without structures.
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DOI:
10.1007/s12026-014-8494-3
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发表时间:
2014-10
影响因子:
4.4
通讯作者:
Gallay PA
Gallay PA
中科院分区:
医学4区
文献类型:
--
作者:
Gawlik K;Gallay PA

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慢性丙型肝炎病毒(HCV)感染是一种进行性疾病,可能最终导致肝硬化,并最终导致肝细胞癌。在过去的几年中,在理解HCV生命周期和开发用于治疗慢性丙型肝炎的小分子化合物方面取得了巨大进展。然而,对HCV组装和颗粒释放的完整理解以及HCV颗粒的详细表征和结构仍然缺失。HCV组装中最重要的事件之一是由核心蛋白驱动的核衣壳形成,核心蛋白可在与病毒RNA相互作用后寡聚化,并由病毒和宿主蛋白协调。尽管越来越多的新的因子参与了HCV的组装过程,但我们并不知道HCV核心蛋白的三维结构或其在核衣壳中的拓扑结构。由于核心蛋白含有负责与细胞膜结合的疏水C-末端结构域,因此HCV病毒体的组装途径可能通过在内质网膜上的共组装进行。最近,新的机制,涉及病毒蛋白和宿主因子在HCV颗粒的形成和出口已被描述。本综述旨在总结我们对HCV组装过程的理解的进展,强调核心蛋白作为病毒颗粒的结构组分,具有与各种细胞组分相互作用的能力,并且是一类新型抗HCV药物开发的有吸引力的潜在靶点。
Chronic hepatitis C virus (HCV) infection is a progressive disease that may end in cirrhosis and, eventually, in hepatocellular carcinoma. In the last several years, tremendous progress has been made in the understanding of HCV life cycle and in the development of small molecule compounds for the treatment of chronic hepatitis C. Nevertheless, the complete understanding of HCV assembly and particle release as well as the detailed characterization and structure of HCV particles are still missing. One of the most important events in the HCV assembly is the nucleocapsid formation that is driven by the core protein, which can oligomerize upon interaction with viral RNA, and is orchestrated by viral and host proteins. Despite a growing number of identified new factors involved in HCV assembly process, we do not know the three-dimensional structure of the HCV core protein or its topology in the nucleocapsid. Since the core protein contains a hydrophobic C-terminal domain responsible for the binding to cellular membranes, the assembly pathway of HCV virions might proceed via co-assembly at endoplasmic reticulum membranes. Recently, the new mechanisms involving viral proteins and host factors in HCV particle formation and egress have been described. The present review aims to summarize the advances in our understanding of the HCV assembly process with an emphasis of the core protein as a structural component of virus particles possessing the ability to interact with a variety of cellular components and being an attractive potential target for the development of a novel class of anti-HCV agents.
DOI: 10.1007/s12026-011-8263-5
发表时间: 2012-06
影响因子: 4.4
作者:
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DOI: 10.1371/journal.ppat.1002302
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发表时间: 2006-08-04
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DOI: 10.1016/j.str.2004.04.024
发表时间: 2004-07
期刊: Structure (London, England : 1993)
影响因子: --
作者:
Dokland T;Walsh M;Mackenzie JM;Khromykh AA;Ee KH;Wang S
通讯作者: Wang S